Department of Neurology and Clinical Neurophysiology, St. Olav's Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.

3

Department of Medical Genetics, Oslo University Hospital, University of Oslo, Oslo, Norway.

4

National Centre for Rare Epilepsy-related Disorders, Oslo University Hospital, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, University of Oslo, Oslo, Norway.

Abstract

Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy with a heterogeneous etiology. In this study, we aimed to explore the role of CHD2 in LGS, as CHD2 mutations have been described recently in various epileptic encephalopathies. We have previously identified one patient with a large deletion affecting the CHD2 gene in a group of 22 patients with LGS or LGS-like epilepsy. In the remaining 17 patients without known etiology, Sanger sequencing revealed a de novo 1-bp duplication in the CHD2 gene in another patient. This mutation leads to a frameshift and, consequently, a premature stop codon 49bp downstream of the mutation. The patient had prominent myoclonic seizures and photosensitivity, thus, sharing phenotypic features with previously reported patients with CHD2-related epilepsy. In our original material of 22 patients with LGS features, we have now found two (9%) with mutations in the CHD2 gene. Our findings suggest that CHD2 mutations are important in the etiological spectrum of LGS.